Worm Breeder's Gazette 15(3): e3 (June 1, 1998)
These abstracts should not be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.
University of Pennsylvania, Department of Cell and Developmental Biology, School of Medicine, Philadelphia, PA 19104-6058
We are investigating the functions of mup-4, a member of a new family of genes, that mediate cell-cell and/or cell-matrix interactions in Caenorhabditis elegans. The mup-4 and mua-3 genes (J. Plenefisch and E. Hedgecock, pers. comm.) have recently been cloned and are shown to be related proteins. Mutants for these genes show related, but distinct phenotypes: mup-4 mutants have defects in embryonic epidermal integrity and muscle position (2), whereas mua-3 mutants, identified by us (1, 2), as well as by J. Plenefisch and E. Hedgecock (pers. comm.), display muscle position defects that occur during larval stages. mup-4 and mua-3 both encode large transmembrane proteins, which include large novel intracellular domains (largely unrelated between the two) and an extracellular domain containing many EGF-like repeats, a type XII collagen motif, and a shared, novel twice-repeated sequence (4). MUA-3 is larger and includes more EGF-like repeats as well as some LDL-like repeats. Although MUP-4 and MUA-3 represent a novel class of proteins, they are similar to many other extracellular matrix (ECM), cell adhesion and cell signaling molecules in that they have a complex modular structure. For example, the combination of EGF-like repeats between type XII collagen-like elements has been observed in vertebrate collagen matrix protein (CMP), present at tendons, but CMP is a secreted ECM protein. The specific functions of these ECM domains, included in MUA-3 and MUP-4, are poorly understood (e.g., 3). Thus, based on its predicted protein domain structure and mutant phenotype, MUP-4 could function as a signal, a receptor, and/or a cell adhesion molecule. One possibility is that MUP-4 mediates cell-cell adhesion and/or signaling between neighboring hypodermal cells, the extracellular domains mediating interactions with adjacent hypodermal cell proteins, and the intracellular domains functioning to anchor or signal to cytoskeletal structures. Another possibility is that MUP-4, through the collagen XII domains, interacts directly with the ECM, either basally to the basement membrane and/or apically to the cuticle, which then would function to anchor the hypodermis to the ECM and directly or indirectly maintain muscle attachments. It is also possible that MUP-4 mediates several of the above functions via its modular and complex structure. We are currently testing these hypotheses by: (i) determining the temporal, spatial and subcellular localization of MUP-4; (ii) examining the ultrastructural defects in mup-4 mutants; and (iii) testing for genetic interactions with mutations in ECM proteins (e.g., perlecan, type IV collagens, cuticular collagens), adhesion proteins (e.g., catenins/cadherins), and muscle attachment proteins (e.g., integrins). 1. Bucher, E., and I. Greenwald. 1991. A genetic mosaic screen of essential zygotic genes in Caenorhabditis elegans. Genetics. 128:281-92. 2. Gatewood, B. K., and E. A. Bucher. 1997. The mup-4 locus in Caenorhabditis elegans is essential for hypodermal integrity, organismal morphogenesis and embryonic body wall muscle position. Genetics. 146:165-83. 3. Wagener, R., B. Kobbe, and M. Paulsson. 1997. Primary structure of matrilin-3, a new member of a family of extracellular matrix proteins related to cartilage matrix protein (matrilin-1) and von Wildebrand factor. FEBS Letters. 413:129-134. 4. Wilson, R., R. Ainscough, K. Anderson, C. Baynes, M. Berks, J. Bonfield, J. Burton, M. Connell, T. Copsey, J. Cooper, and et al. 1994. 2.2 Mb of contiguous nucleotide sequence from chromosome III of C. elegans [see comments]. Nature. 368:32-8.